If you have diabetes, your body does not make enough insulin, or the insulin it does make is less effective (insulin resistance). At diagnosis, the pancreas is already 50 per cent less able to produce insulin. The insulin it does make can no longer keep glucagon (a hormone that triggers the liver to make and release glucose) in balance. This means more glucose is released into the blood stream. As well, fewer hormones help regulate glucose in the gut. Muscle and fat cells resist the action of insulin as it works to take glucose into the cells for energy and storage. All of these changes make blood sugar rise.
Medication used for type 2 diabetes targets these changes. If you are taking medication for the first time, metformin is the most likely one to be prescribed. It is the first choice of oral drug recommended to treat and prevent diabetes in the 2013 Canadian Diabetes Association guidelines. Along with lifestyle changes, it is usually prescribed at diagnosis. When the A1C at diagnosis is greater than 8.5 per cent, metformin may be combined with another drug such as insulin. Other medications below are listed based on drug class, and not in any order of preference.
Biguanide – Known as metformin, this is usually the first drug your doctor will recommend. It slows down the release of sugar from the liver and reduces insulin resistance. Metformin will not cause hypoglycemia (low blood sugar). It is taken with food, and started at a low dose (such as 500 mg once a day), then gradually increased. Slowly raising the dose means side effects of nausea, vomiting and diarrhea are less likely to occur, or will disappear over a two week period. The dose is increased every two weeks until the morning blood sugar is less than 7.0 mmol/L. Metformin takes two weeks to work. It primarily affects the fasting blood glucose reading. The maximum dose is 2500 mg per day. Using it for a long time may lower your vitamin B12 levels. If you are scheduled to have an x-ray involving dyes, or for surgery, stop taking Metformin 24 hours before the procedure.
Sulfonylureas – Glyburide, gliclazide (Diamicron™) and glimepiride (Amaryl™) make the beta cells in the pancreas release more insulin. They can cause hypoglycemia (blood sugar of less than 4.0 mmol/L). The symptoms include dizziness, drowsiness, sweating, blurred vision, headache, and shaking. To reduce the risk, eat regularly spaced meals and plan for activity. Since the effect of gliclazide and glimepiride is glucose-dependent (related to what your actual blood glucose is), they are less likely to result in hypoglycemia. If it does occur, treat with 15 gm of fast acting carbohydrate such as four dextrose tablets or half a cup of juice. Wait 15 minutes and check blood sugar again. Weight gain is another possible side effect.
Meglitinides – Repaglinide (Gluconorm™) and nateglinide (Starlix™) also encourage the pancreas to release more insulin. They are fast and short-acting, and cause less hypoglycemia than the sulfonylureas. They may cause weight gain. Only take meglitinides just before eating a meal. They allow greater flexibility in meal planning, and are good for irregular eaters.
Alpha-glucosidase inhibitor acarbose (Glucobay™) – This medication slows the rate at which carbohydrates are absorbed, allowing available insulin to work better. Take it along with the first bite of the meal. Starting with a low dose and slowly increasing it will reduce the side effects of gas and intestinal bloating. While it does not cause hypoglycemia by itself, if you take another a drug that does, the hypoglycemia must only be treated with dextrose.
Thiazolidinediones (TZDs) rosiglitazone (Avandia™) and pioglitazone (Actos™) – These medications lower insulin resistance, allowing insulin to take glucose into the muscle and fat cells. While TZDs do not cause hypoglycemia, they can result in fluid retention and weight gain. It may take four to 12 weeks for blood glucose lowering to be evident. If you use insulin or have a heart condition, you should not take TZDs. These medications are rarely prescribed, as studies link them to an increased risk of cardiovascular events and fractures.
DPP-4 inhibitors Sitagliptin (Januvia™), Saxagliptin (Onglyza™) and Linagliptin (Trajenta™) – After a meal, a naturally occurring gut hormone (glucagon-like peptide 1, or GLP1), is released in the intestines. The DPP-4 enzyme inactivates it within two to seven minutes. DPP-4 inhibitors allow GLP1 to work longer. They enhance two actions of GLP1 – the glucose-dependent release of insulin and the suppression of glucagon. Both actions take place in the pancreas. DPP-4 inhibitors do not cause hypoglycemia. Most people do not experience any side effects, although upper respiratory tract infections and a stuffy nose are possible.
GLP1 analogues: exenatide (Byetta™) and liraglutide (Victoza™) – These injected drugs mimic the full action of the hormone GLP1 and resist breakdown by the DPP-4 enzyme. People with type 2 diabetes have less GLP1 hormone than those without diabetes. Depending on your blood sugar level, GLP1 can enhance the release of insulin and suppress the release of glucagon from the pancreas. It can also delay stomach emptying so carbohydrates are absorbed more slowly, allowing you to realize when you are full and stop eating. GLP1 analogues may cause weight loss, commonly about four to six pounds although it can be more significant. Exenatide is injected twice daily up to 60 minutes before a meal. Liraglutide is injected once daily without regard to meals. The main side effects are gastrointestinal. With exenatide, nausea has been reported in 36 per cent of patients on the 5 ug dose and 45 per cent on the 10 ug dose. With Liraglutide, the nausea usually diminishes within four weeks. Eating smaller, more frequent meals can help reduce it. GLP1 analogues have been associated with pancreatitis. One symptom is persistent severe abdominal pain, sometimes radiating towards the back and possibly accompanied with vomiting. If you have a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome, do not use these medications.
SGLT2 inhibitors – A brand new drug class for treating type 2 diabetes has just arrived in Canada, with the first drug to market being canagliflozin (Invokana™). SGLT 2 inhibitors work on the kidney to increase the amount that passes into the urine. Canagliflozin does not cause hypoglycemia. The most common side effects are genital fungal infections, urinary tract infections and increased urination. A risk of dehydration is higher in those with low blood pressure, on blood pressure medication including diuretics (water pills), on a low salt diet, with kidney problems or over age 65. Take canagliflozin once daily before the first meal of the day.
Medication alone cannot fully control diabetes. Lifestyle changes, a healthy portion-controlled meal plan and increased physical activity are also key. All the medications discussed here lower the A1C an average of one per cent. Some are combined with metformin, to make the two easier to take together.
Diabetes is progressive. Over time, the pancreas becomes less able to produce insulin. Eventually an estimated 60 per cent of patients will require insulin. While insulin therapy can seem frightening, it is really just another treatment choice. If A1C is greater than 8.5 per cent at diagnosis or during any stage of the disease, insulin can be used. New injection devices, smaller thinner needles and advances in formulation make insulin a safe choice.
Diabetes treatment and medications must be tailored to your personal characteristics. Your blood glucose level, risk of hypoglycemia, existing conditions, weight and preferences are all taken into consideration. When selecting a new medication, your risk of hypoglycemia, the drug’s effect on your weight, the amount of blood glucose lowering required, potential side effects and cost all should be considered. For more information about any medication, talk to your pharmacist.